Protein-coding gene in the species Homo sapiens
Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A), also known as ODIN, is a
protein that in humans is encoded by the ANKS1A
gene on
chromosome 6 .
[5]
[6]
It is ubiquitously expressed in many tissues and cell types.
[7] ODIN is known to regulate the
epidermal growth factor receptor (EGFR) and
EphA receptor signaling pathways.
[8] As a
Src family kinase target, ODIN has been implicated in the development of
cancer .
[9] The ANKS1A gene also contains one of 27
SNPs associated with increased risk of
coronary artery disease .
[10]
The ANKS1A gene resides on chromosome 6 at the band 6p21.31 and includes 29
exons .
[6] This gene produces 2
isoforms through
alternative splicing .
[11]
ODIN is a member of the ankyrin repeat and sterile alpha motif domain-containing (ANKS) family and contains 6
ankyrin repeats , 1
phosphotyrosine binding (PTD) domain , and 2
tandem sterile alpha motif (SAM) domains.
[11]
[12] The first SAM domain binds to the SAM domain of the
EphA2 receptor by adopting a mid-loop/end-helix conformation and may regulate EphA2
endocytosis .
[12]
[13]
ODIN is widely expressed in tissues including
heart ,
brain ,
placenta ,
lung ,
liver ,
skeletal muscle ,
kidney and
pancreas .
[14] ODIN has been identified as one of the
tyrosine phosphorylated proteins induced by activating
epidermal growth factor or
platelet-derived growth factor receptor
tyrosine kinases .
[14] ODIN is involved in negative regulation of the
EGFR signaling pathway.
[8] It is reported that ODIN level is correlated with the degree of increased EGF-induced EGFR trafficking to recycle
endosomes and recycle back to the
cell surface , suggesting a role in EGFR recycling.
[15] Furthermore, ODIN serves as a key adaptor protein regulating the EphA receptor signaling pathway, which is critical for regulating
EphA8 -mediated
cell migration and
neurite outgrowth .
[16]
[17] It has been demonstrated that deletion of the
phosphotyrosine binding domain in ODIN will lead to an immaturely developed
subcommissural organ (SCO) with a severe midbrain
hydrocephalic phenotype, which means ODIN also plays a role in the proper development of the SCO and in
ependymal cells in the
cerebral aqueduct .
[18]
As a novel target of
Src family kinases , which are implicated in the development of some colorectal cancers, ODIN may be involved in cancer cell signaling mechanisms.
[19] In a study, 64
colorectal cancer cell lines were tested for their expression of Lck.
Mass spectrometric analyses of Lck-purified proteins subsequently identified several proteins readily known as SFK kinase substrates, including cortactin, Tom1L1 (SRCASM), GIT1, vimentin and AFAP1L2 (XB130). Additional proteins previously reported as substrates of other
tyrosine kinases were also detected, including ODIN. ODIN was further analyzed and found to contain substantially less pY upon inhibition of SFK activity in SW620 cells, indicating that it is a formerly unknown SFK target in colorectal carcinoma cells.
[19] Furthermore, it has been found that ODIN regulates COPII-mediated anterograde transport of receptor tyrosine kinases, which is a critical mechanism in the process of tumor genesis.
[20]
A multi-locus genetic risk score study based on a combination of 27
loci , including the ANKS1A gene, identified individuals at increased risk for both incident and recurrent
coronary artery disease events, as well as an enhanced clinical benefit from
statin therapy. The study was based on a community
cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).
[10]
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000064999 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000024219 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N (October 1996).
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^
a
b
"Entrez Gene: ANKS1A ankyrin repeat and sterile alpha motif domain containing 1A" .
^
"BioGPS - your Gene Portal System" . biogps.org . Retrieved 2016-10-10 . [
permanent dead link ]
^
a
b Kristiansen TZ, Nielsen MM, Blagoev B, Pandey A, Mann M (August 2004). "Mouse embryonic fibroblasts derived from Odin deficient mice display a hyperproliiferative phenotype". DNA Research . 11 (4): 285–92.
PMID
15500253 .
^ Emaduddin M, Edelmann MJ, Kessler BM, Feller SM (2008-01-01).
"Odin (ANKS1A) is a Src family kinase target in colorectal cancer cells" . Cell Communication and Signaling . 6 : 7.
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10.1186/1478-811X-6-7 .
PMC
2584000 .
PMID
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^
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b
"ANKS1A - Ankyrin repeat and SAM domain-containing protein 1A - Homo sapiens (Human) - ANKS1A gene & protein" . www.uniprot.org . Retrieved 2016-10-10 .
^
a
b Mercurio FA, Marasco D, Pirone L, Pedone EM, Pellecchia M, Leone M (March 2012).
"Solution structure of the first Sam domain of Odin and binding studies with the EphA2 receptor" . Biochemistry . 51 (10): 2136–45.
doi :
10.1021/bi300141h .
PMC
3319784 .
PMID
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^ Mercurio FA, Di Natale C, Pirone L, Scognamiglio PL, Marasco D, Pedone EM, Saviano M, Leone M (July 2015). "Peptide Fragments of Odin-Sam1: Conformational Analysis and Interaction Studies with EphA2-Sam". ChemBioChem . 16 (11): 1629–36.
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PMID
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^
a
b Pandey A, Blagoev B, Kratchmarova I, Fernandez M, Nielsen M, Kristiansen TZ, Ohara O, Podtelejnikov AV, Roche S, Lodish HF, Mann M (November 2002).
"Cloning of a novel phosphotyrosine binding domain containing molecule, Odin, involved in signaling by receptor tyrosine kinases" . Oncogene . 21 (52): 8029–36.
doi :
10.1038/sj.onc.1205988 .
PMID
12439753 .
^ Tong J, Sydorskyy Y, St-Germain JR, Taylor P, Tsao MS, Moran MF (2013-01-01).
"Odin (ANKS1A) modulates EGF receptor recycling and stability" . PLOS ONE . 8 (6): e64817.
Bibcode :
2013PLoSO...864817T .
doi :
10.1371/journal.pone.0064817 .
PMC
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PMID
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^ Kim J, Lee H, Kim Y, Yoo S, Park E, Park S (April 2010).
"The SAM domains of Anks family proteins are critically involved in modulating the degradation of EphA receptors" . Molecular and Cellular Biology . 30 (7): 1582–92.
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10.1128/MCB.01605-09 .
PMC
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PMID
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^ Shin J, Gu C, Park E, Park S (December 2007).
"Identification of phosphotyrosine binding domain-containing proteins as novel downstream targets of the EphA8 signaling function" . Molecular and Cellular Biology . 27 (23): 8113–26.
doi :
10.1128/MCB.00794-07 .
PMC
2169194 .
PMID
17875921 .
^ Park S, Lee H, Park S (May 2015).
"In Vivo Expression of the PTB-deleted Odin Mutant Results in Hydrocephalus" . Molecules and Cells . 38 (5): 426–31.
doi :
10.14348/molcells.2015.2288 .
PMC
4443284 .
PMID
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^
a
b Emaduddin M, Edelmann MJ, Kessler BM, Feller SM (October 2008).
"Odin (ANKS1A) is a Src family kinase target in colorectal cancer cells" . Cell Communication and Signaling . 6 : 7.
doi :
10.1186/1478-811X-6-7 .
PMC
2584000 .
PMID
18844995 .
^ Lee H, Noh H, Mun J, Gu C, Sever S, Park S (September 2016).
"Anks1a regulates COPII-mediated anterograde transport of receptor tyrosine kinases critical for tumorigenesis" . Nature Communications . 7 : 12799.
Bibcode :
2016NatCo...712799L .
doi :
10.1038/ncomms12799 .
PMC
5027278 .
PMID
27619642 .
Human
ANKS1A genome location and
ANKS1A gene details page in the
UCSC Genome Browser .
Overview of all the structural information available in the
PDB for
UniProt :
Q92625 (Human Ankyrin repeat and SAM domain-containing protein 1A) at the
PDBe-KB .
Overview of all the structural information available in the
PDB for
UniProt :
P59672 (Mouse Ankyrin repeat and SAM domain-containing protein 1A) at the
PDBe-KB .
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"Cloning of a novel phosphotyrosine binding domain containing molecule, Odin, involved in signaling by receptor tyrosine kinases" . Oncogene . 21 (52): 8029–36.
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